Multiscale Imaging of Spontaneous Activity in Cortex: Mechanisms, Development and Function

 描述（由申请人提供）：该RFA的目的是促进实验，分析和理论能力的整合，以检查神经回路和系统。这项建议是高度响应RFA的，因为它连接了几个不同的神经科学实验室，以开发新的技术，提供同时多状态成像，并应用这些技术来检查哺乳动物皮层神经元动力学如何作为大脑状态和发育的函数而变化。配对成像模式将弥合从单个神经元的成像活动到全脑回路水平分析的差距。不同的尺度将与一个综合模型联系起来，以便每一级实验都能相互借鉴。我们将开发的技术，允许同时单细胞（双光子）Ca2+成像的局部电路和整个新皮层的皮层范围内的介观（单光子）Ca2+成像。在相同动物的单独配对研究中，我们将使用全脑功能MRI开发跨皮质的同步介观Ca2+成像。全皮层介观Ca2+成像代表了由PI之一（Crair）开发的创新技术，该技术使用在所有神经元或选定神经元群体中表达遗传编码Ca2+指示剂（GCaMP6）的小鼠，以允许在完整的未麻醉发育小鼠大脑中跨皮层进行局部神经元和经颅群体水平介观尺度成像。这种Ca2+成像技术将使我们能够直接将单细胞成像与整个皮层和整个大脑的总回路水平活动联系起来。提出了一种综合模型来连接这些不同的模式，以了解宏观回路变化的神经源以及通过发育和行为大脑状态影响该组织的因素。这项工作是创新的新的钙离子成像策略，以进一步发展，并在成对的规模成像的设计，以建立单神经元活动和电路水平的组织之间的联系。这项工作的意义在于，它将提供一套工具，用于详细研究特定神经元细胞群对健康发育和疾病模型中脑回路功能组织的影响。它的意义还在于，将获得对神经元活动的来源和流动的新见解，这将提高我们对指导发育中的大脑中的自组织及其通过大脑状态的动态调节的原则的理解。

 DESCRIPTION (provided by applicant): The purpose of this RFA is to promote the integration of experimental, analytic and theoretical capabilities for the examination of neural circuits and systems. This proposal is highly responsive to the RFA in that it links several different neuroscience labs to develop new technologies that provide for simultaneous multistate imaging and applies these technologies to the examination of how neuronal dynamics in mammalian cortex varies as a function of brain state and development. Paired imaging modalities will bridge the gap from imaging activity in individual neurons to whole brain circuit level analyses. The different scales will be linked with a comprehensive model such that each level of experimentation can inform the other. We will develop the technology to allow simultaneous single cell (two-photon) Ca2+ imaging of a local circuit and cortex-wide mesoscopic (single-photon) Ca2+ imaging across the entire neocortex. In separate paired studies in the same animals we will develop simultaneous mesoscopic Ca2+ imaging across the cortex with whole-brain functional MRI. Whole cortex mesoscopic Ca2+ imaging represents an innovative technology developed by one of the PIs (Crair) that uses mice expressing a genetically encoded Ca2+ indicator (GCaMP6) in all neurons or in select populations of neurons to allow both local neuronal and transcranial population level mesoscopic scale imaging across the cortex in the intact, unanesthetized developing mouse brain. This Ca2+ imaging technique will allow us to directly link single cell imaging to gross circuit level activity across the cortex and whole brain An integrative model is proposed to link these different modalities in order to understand the neural source of macroscopic circuit changes and the factors that influence this organization through development and as a function of behavioral brain state. This work is innovative in the novel Ca2+ imaging strategies to be further developed, and in the design of paired scale imaging to establish links between single neuron activity and circuit level organization. The work is significant in that it will provide a set of tools for detailed investigations of the impact of specific neuronal cell populations on brain circuit functional organization in healthy development and disease models. It is also significant in that new insights into the source and flow of neuronal activity will be obtained that will improve our understanding of the principles guiding self-organization in the developing brain and its dynamic modulation by brain state.